MLL translocations specify a distinct gene expression profile, distinguishing a unique leukemia

Abstract

The present invention relates to the diagnosis of mixed lineage leukemia (MLL), acute lymphoblastic leukemia (ALL), and acute myelogenous leukemia (AML) according to the gene expression profile of a sample from an individual, as well as to methods of therapy and screening that utilize the genes identified herein as targets.

1 . A method of identifying a candidate compound for use in treating mixed lineage leukemia comprising: 
 a) contacting a cell sample with a candidate compound, wherein the cell is selected from the group consisting of mononuclear blood cells and bone marrow cells; and    b) detecting an alteration of a gene expression profile of a gene expression product from at least one informative gene from the cell sample,    wherein a candidate compound that increases the gene expression profile of at least one informative gene which is decreased in mixed lineage leukemia or decreases the gene expression profile of at least one informative gene which is increased in mixed lineage leukemia, is a candidate compound for use in treating mixed lineage leukemia.    
     
     
         2 . The method of  claim 1 , wherein the candidate compound decreases the gene expression profile of at least one informative gene which is increased in mixed lineage leukemia wherein said gene selected from the group consisting of FLT3, MEIS1, and HoxA9.  
     
     
         3 . A method of identifying a compound for use in treating mixed lineage leukemia, comprising: 
 a) determining a gene expression profile of a gene expression product from at least one informative gene from one or more cells selected from the group consisting of mononuclear blood cells and bone marrow cells of an individual with mixed lineage leukemia;    b) administering a candidate compound to the individual;    c) determining a gene expression profile of the gene expression product(s) of step a) from one or more cells selected from the group consisting of mononuclear blood cells and bone marrow cells from the individual of step b); and    d) comparing the gene expression profiles of step a) to the gene expression profile of step c),    wherein if the gene expression profile from the individual after administration of the agent is correlated with effective treatment of mixed lineage leukemia, then the candidate compound is a compound for use in treating mixed lineage leukemia.    
     
     
         4 . The method of  claim 3 , wherein the candidate compound decreases the gene expression profile of at least one informative gene which is increased in mixed lineage leukemia wherein said gene selected from the group consisting of FLT3, MEIS1, and HoxA9.  
     
     
         5 . A method of identifying a candidate compound for use in treating acute lymphoblastic leukemia, comprising: 
 a) contacting a cell sample with a candidate compound, wherein the cell is selected from the group consisting of mononuclear blood cells and bone marrow cells; and    b) detecting an alteration of a gene expression profile of a gene expression product from at least one informative gene from the cell sample,    wherein a candidate compound that increases the gene expression profile of at least one informative gene which is decreased in acute lymphoblastic leukemia or decreases the gene expression profile of at least one informative gene which is increased in acute lymphoblastic leukemia, is a candidate compound for use in treating mixed lineage leukemia acute lymphoblastic leukemia.    
     
     
         6 . A method of identifying a compound for use in treating acute lymphoblastic leukemia, comprising: 
 a) determining a gene expression profile of a gene expression product from at least one informative gene from one or more cells selected from the group consisting of mononuclear blood cells and bone marrow cells of an individual with acute lymphoblastic leukemia;    b) administering a candidate compound to the individual;    c) determining a gene expression profile of the gene expression product(s) of step a) from one or more cells selected from the group consisting of mononuclear blood cells and bone marrow cells from the individual of step b); and    d) comparing the gene expression profiles of step a) to the gene expression profile of step c),    wherein if the gene expression profile from the individual after administration of the agent is correlated with effective treatment of acute lymphoblastic leukemia, then the candidate compound is a compound for use in treating acute lymphoblastic leukemia.    
     
     
         7 . A method of identifying a candidate compound for use in treating acute myelogenous leukemia comprising: 
 a) contacting a cell sample with a candidate compound, wherein the cell is selected from the group consisting of mononuclear blood cells and bone marrow cells; and    b) detecting an alteration of a gene expression profile of a gene expression product from at least one informative gene from the cell sample,    wherein a candidate compound that increases the gene expression profile of at least one informative gene which is decreased in acute myelogenous leukemia or decreases the gene expression profile of at least one informative gene which is increased in acute myelogenous leukemia, is a candidate compound for use in treating acute myelogenous leukemia.    
     
     
         8 . A method of identifying a compound for use in treating acute myelogenous leukemia, comprising: 
 a) determining a gene expression profile of a gene expression product from at least one informative gene from one or more cells selected from the group consisting of mononuclear blood cells and bone marrow cells of an individual with acute myelogenous leukemia;    b) administering a candidate compound to the individual;    c) determining a gene expression profile of the gene expression product(s) of step a) from one or more cells selected from the group consisting of mononuclear blood cells and bone marrow cells from the individual of step b); and    d) comparing the gene expression profiles of step a) to the gene expression profile of step c),    wherein if the gene expression profile from the individual after administration of the agent is correlated with effective treatment of acute myelogenous leukemia, then the candidate compound is a compound for use in treating acute myelogenous leukemia.